Time and frequency domain analysis of heart rate variability in cattle affected by bovine spongiform encephalopathy

Abstract

BackgroundHeart rate variability (HRV) analysis is a method to assess the function of the autonomic nervous system. Brainstem nuclei that influence HRV are affected by vacuolar changes and accumulation of disease-associated prion protein (PrPd) in bovine spongiform encephalopathy (BSE) resulting in clinical signs suggestive of an increased parasympathetic tone. It was hypothesised that BSE in cattle causes changes in the autonomic nervous system; this was tested by comparing HRV indices derived from 1048 electrocardiograms, which were recorded from 51 naturally or experimentally infected cattle with BSE confirmed by postmortem tests, 321 clinical suspect cases or cattle inoculated with potentially infectious tissue without disease confirmation and 78 BSE-free control cattle.FindingsStatistically significant differences were found for low or high frequency power, their normalised values and ratio when the last recording prior to cull or repeated recordings were compared but only between male and female cattle of the three groups and not between groups of the same gender, even though BSE cases of each gender appeared to be more nervous during the recording. The same findings were made for heart rate, deviation from the mean RR interval and vasovagal tonus index when repeated recordings were compared. BSE cases with severe vacuolar changes in the parasympathetic nucleus of the vagus nerve had a significantly lower low:high frequency power ratio but not a lower heart rate than BSE cases with mild vacuolation, whereas severity of vacuolar changes in the solitary tract nucleus or intensity of PrPd accumulation in both nuclei did not appear to have any affect on either index. Abnormalities in the electrocardiogram were detected in 3% of the recordings irrespective of the BSE status; sinus arrhythmia was present in 93% of the remaining recordings.ConclusionsHRV analysis was not useful to distinguish BSE-positive from BSE-negative cattle grouped by gender, and HRV indices appeared to be mainly influenced by gender. There is agreement with earlier studies that vacuolar changes in the brainstem may be associated with an increased parasympathetic tone in BSE and that abnormalities in an electrocardiogram can be detected in cattle without evidence of heart disease.

Experimental H-type and L-type bovine spongiform encephalopathy in cattle: observation of two clinical syndromes and diagnostic challenges

“…None of the affected cattle were bradycardic at clinical end-stage (heart rate not determined for case H-2) as reported separately [33] but unexpected startle was observed. Hence, atypical BSE should be considered as differential diagnosis in any recumbent animal, which - based on naturally occurring cases [17] - is 8 years of age or older and has a history of or presents with over-reactivity to various external stimuli.…”

Identification of clinical target areas in the brainstem of prion‐infected mice

“…Involvement of the vagus nerve and the NTS has been reported also in natural and experimental cases of BSE in cattle, confirming the vagal parasympathetic fibre as a route for spreading of prion from periphery to the CNS [62,63]. Bradycardia, as an effect of increased vagal tone [64,65] and heart rate variability [66], has been reported in cattle orally challenged with BSE, but ECG variability does not correlate with evidences of heart disease [67]. In a murine model of BSE, early vulnerability of the central serotonergic system was supported by behavioural and anatomical-pathological observation [68].…”

The pathological and molecular but not clinical phenotypes are maintained after second passage of experimental atypical bovine spongiform encephalopathy in cattle

“…Although based on only one animal, it does not support the hypothesis that affected animals become duller as the disease progresses, even though lesions in the brain become more widespread and may affect the forebrain, diencephalon and the reticular activating system in the brainstem, which are associated with an altered state of alertness [ 33 ]. The lack of a clear relationship between morphological changes or PrP d accumulation and clinical signs has been reported before in large animals affected by prion diseases [ 34 - 36 ]. There were no obvious differences in the neuropathology of individual cattle that could explain the difference in the clinical presentation and there was also no discernable molecular profile difference between the two L-type recipients (presence or absence of dullness).…”